The objective is to determine the susceptibility of the nude, athymic mouse to viral parasitic, and bacterial diseases, and to define the role of the thymus activated "T" lymphocytes in susceptibility and pathogenesis of infectious diseases. Weanling mice are transferred directly from the Building 14G barrier to presterilized, germfree isolators. Protecting this highly susceptible animal from the conventional environment with the flexible plastic isolator system has proven extremely successful. Many nudes, who have a 4-month life span in conventional animal quarters, are still surviving after 15 months in our isolator system. This project originated as an attempt to infect nude mice with human hepatitis A and hepatitis B. Serum from a human known to be infected with "B", and from a chimpanzee known to be infected with "A" was injected I.V. into separate groups of animals. After over 12 months of testing for the antigen and antibody for B and for liver enzyme changes associated with A infections it was concluded that, despite their lack of a cellular immune response, the nude, athymic mouse is not susceptible to human viral hepatitis. In collaboration with Johns Hopkins University, nude mice in isolators were also exposed to known numbers of infectious Schistosome larvae. This congenital, athymic state, with its resuling lack of cell mediated immunity in the nude mouse, may be one of the most significant events in the evaluation of animal models for human disease. It must be defined in a number of areas to realize its potential and limitations in biomedical research.